The proposed research will employ nuclear magnetic resonance (nmr) measurements of specifically labelled proteins to obtain details of enzyme conformation and mechanism including the properties of individual amino acid side chains and the consequences of conformational changes which accompany substrate binding, metal ion binding, and subunit interactions. The enzymes to be studied include alpha-lytic protease containing (gamma-13C)-histidine, horse liver alcohol dehydrogenase labelled chemically with 19F, and tryptophan synthetase alpha subunit labelled chemically with 13C. In addition, 3H-labelled enzymes will be prepared in order to assess the utility of 3H nmr in investigations of macromolecular structure.